Combination treatment of intravenous immunoglobulin and cultivated oral mucosal epithelial transplantation for ocular cicatricial pemphigoid.
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Cicatrix↗
Biomedical subjects
M Uchino
Publications and source records attributed to M Uchino.
Iatrogenic amyloid neuropathy in a Japanese patient after sequential liver transplantation.
A 57-year-old woman in Japan, the first recipient of part of a liver from a 58-year-old man with familial amyloidotic polyneuropathy (FAP) amyloidogenic transthyretin Val30Met who had had sensorimotor polyneuropathy in the lower limbs for 3 years, started to develop sensory neuropathy 7 years after transplantation. Before the July 1998 sequential transplantation, she had been in a hepatic coma at the terminal stage of primary biliary cirrhosis and waiting for deceased donor liver transplantation. In September 2004, biopsy samples of her duodenum first showed amyloid deposition. Although biopsy materials in 2005 and 2006 showed no changes in amyloid deposition, decreased temperature sensation and pain in fingertips and toes were detected at a neurologic examination in March 2006. Thus, clinical symptoms of FAP appeared about 2 years after amyloid deposition started. Nerve conduction velocity studies revealed mild to moderate axonal sensory polyneuropathy without demyelination. Our findings confirmed iatrogenic sensory neuropathy induced by amyloid deposition 7 years after sequential liver transplantation.
Amyloid Neuropathies, Familial↗
Intermittent oro-esophageal tube feeding in acute stroke patients -- a pilot study.
OBJECTIVE: Acute stroke patients with dysphagia are usually fed by nasogastric tube. However, this method sometimes causes pneumonia or diarrhea. We investigated the use of a new feeding procedure called intermittent oro-esophageal (IOE) tube feeding in acute stroke patients with severe dysphagia. MATERIALS AND METHODS: The IOE method was used in 13 acute stroke patients (68 +/- 14 years old; 12 had a brainstem infarction), who were alert, but had severe dysphagia and a weak pharyngeal reflex. IOE tube feeding was carried out as follows. A feeding tube was passed orally into the lower portion of the esophagus, food supplements were administered through the tube at a rate of approximately 50 ml/min, and the tube was removed after finishing the supplement infusion. RESULTS: We found that the IOE method had the following advantages: (i) IOE feeding took approximately 15 min; (ii) potentially reduced a risk of complications such as pneumonia and diarrhea; and (iii) oral tube insertion stimulated the oral cavity and pharynx, which may improve the swallowing function. However, the IOE feeding method should not be used in patients who: (i) could not understand the IOE procedure; (ii) had an esophageal hiatal hernia or incomplete peristalsis of the esophagus, as such patients are at risk of having the supplement reflux into the oral cavity. CONCLUSION: The IOE feeding method may be one of the alternatives to continuous nasogastric tube feeding in acute stroke patients with severe dysphagia, who are alert.
Acute Disease↗
Neuroradiologic and clinicopathologic features of oculoleptomeningeal type amyloidosis.
OBJECTIVE: To clarify the pathogenesis of leptomeningeal amyloidosis in familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C (FAP ATTR Y114C). METHODS: The authors analyzed eight FAP ATTR Y114C patients. Six patients showed CNS symptoms associated with leptomeningeal amyloidosis. To examine the function of the blood-CSF barrier and blood-brain barrier (BBB), the authors performed CSF and MRI studies. The authors also performed a histopathologic study of autopsy specimens to examine the distribution of amyloid deposition in the CNS. RESULTS: CSF study showed high total protein concentrations and increased albumin CSF/serum concentration quotients (Qalb; an indication of blood-CSF barrier function). MRI with gadolinium (Gd) revealed enhancement from brainstem to spinal cord. Serial brain MRI studies with FLAIR images after Gd administration showed Gd leakage into the subarachnoid space (two patients). These findings suggested the blood-CSF barrier and BBB dysfunctions. Constructive interference in steady state (CISS) three-dimensional Fourier transformation (CISS-3DFT) sequence analysis demonstrated amyloid-induced funiculus structures joining the spinal cord and dura mater (one patient). Histopathologic study revealed intense amyloid deposition in leptomeninges, vessel walls, and parenchyma in spinal cord and the brain. These distributions of amyloid deposition are unique compared to other TTR related leptomeningeal amyloidosis. CONCLUSIONS: Patients with familial amyloidotic polyneuropathy amyloidogenic transthyretin Y114C had CNS disorders related to amyloid deposition in leptomeninges, vessel walls, and parenchyma in spinal cord and the brain. The pathogenesis of CNS disorders may reflect disruption of the blood-CSF barrier and blood-brain barrier by amyloid deposition.
Adult↗
Fusiform aneurysm of the vertebral artery presenting with hemifacial spasm treated by microvascular decompression.
We report a rare case of symptomatic hemifacial spasm caused by a fusiform vertebral artery aneurysm. A 59-year-old woman presented with left hemifacial spasm of 18 months duration. Magnetic resonance imaging showed an enlarged a fusiform aneurysm of the left vertebral artery which compressed the seventh cranial nerve at its exit from the caudal pons. Microvascular decompression of the facial nerve with moving of the aneurysm resulted in complete relief of the hemifacial spasm. No enlargement of the aneurysm was shown on follow-up for a period of 6 years.
Aneurysm↗
Animal model of oculopharyngeal muscular dystrophy.
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset polyalanine disorder characterized clinically by progressive ptosis, dysphagia, and limb weakness and pathological hallmarked by unique intranuclear inclusions in the muscles. It is caused by heterozygous expansion of a 10-alanine stretch to 12-17 alanine residues in the N-terminus of the poly(A)-binding protein, nuclear 1 (PABPN1). Although PABPN1 is a major component of the inclusions in OPMD, the associated pathogenic mechanism is undetermined. No animal models of OPMD have been discovered in nature; therefore, we generated transgenic mice expressing human PABPN1 (hPABPN1) using a chicken beta-actin (CAG) promoter. While transgenic mice lines expressing normal hPABPN1 did not show myopathic changes, lines expressing high levels of expanded hPABPN1 with a 13-alanine stretch showed myopathy phenotype with aging. The latter mice disclosed intranuclear inclusions consisting of aggregated mutant hPABPN1 and scattered rimmed vacuoles restricted in the muscles. In particular, the nuclear inclusions closely resembled those of OPMD muscles on electron microscopy, and myopathic changes were more prominent in the eyelid and pharyngeal muscles. The results demonstrated that we had established the first transgenic OPMD model mouse. Recently, two other transgenic mice expressing mutated hPABPN1 with a 17-alanine stretch have been generated; however, the transgenic mouse using its natural promoter did not show myopathy phenotype, and the other using the human skeletal actin (HSA1) promoter disclosed quite different intranuclear inclusions from those of human OPMD muscles. Our transgenic OPMD model mouse appears to have more dramatic alterations in myofiber viability, but is useful for elucidating of molecular mechanisms and establishing therapeutic trials.
Actins↗
Ruptured aneurysm at a duplicated middle cerebral artery with accessory middle cerebral artery.
Although many cerebral vascular anomalies are widely recognized, others are less well known or unclassified. Accessory middle cerebral artery (MCA) and duplicated MCA are among uncommon anomalies. We present a very rare case of subarachnoid haemorrhage due to rupture of a saccular aneurysm arising from a duplicated middle cerebral artery which was associated with an accessory middle cerebral artery.
Aneurysm, Ruptured↗
Near-infrared spectrophotoscopy of finger venules in assessment of autonomic dysfunction.
The authors evaluated morphologic changes in the venules of the finger using near-infrared spectrophotoscopy in patients with autonomic dysfunction, such as familial amyloidotic polyneuropathy and multiple-system atrophy. Abnormalities of the venules, such as tortuosity, irregular venous caliber, and microaneurysm-like change, and a linear negative correlation between the degree of orthostatic hypotension and the degree of vasoconstriction of the venules were observed.
Adult↗
DWI abnormalities and clinical characteristics in TIA patients.
OBJECTIVE: To determine the clinical characteristics of diffusion-weighted images (DWIs) in patients with TIA. METHODS: The authors performed prospectively MRI including DWI in 129 consecutively studied patients with TIA (mean age, 67 years; 68% men) within 14 days after TIA onset. They examined the frequency of TIA-related DWI abnormalities and compared the clinical background of patients with and without DWI abnormalities. Using multivariate statistical methods, the authors investigated the independent factors associated with detection of DWI abnormalities. RESULTS: Fifty-seven patients with TIA (44%) had DWI abnormalities (positive group), whereas 72 (56%) had no abnormalities (negative group). Prolonged TIA duration (TIA duration > or = 30 minutes), hemiparesis, monoparesis, disturbance of higher brain function, history of either stroke or TIA, diabetes mellitus, and atrial fibrillation were observed more frequently in the positive group than in the negative group. No difference in other symptoms, vascular risk factors, or emboligenic cardiac and arterial disease was observed between the two groups. A multiple logistic regression model demonstrated that prolonged TIA duration (odds ratio [OR], 3.7; 95% CI, 1.3 to 10.8) and disturbance of higher brain function (OR, 10.2; 95% CI, 2.2 to 46.9) are significant and independent factors in correlating with DWI abnormalities. CONCLUSIONS: TIA-related DWI abnormalities are associated with prolonged duration of TIA and disturbance of higher brain function. More sustained and extensive ischemia may contribute to DWI abnormalities in patients with TIA.
Aged↗
Targeted conversion of the transthyretin gene in vitro and in vivo.
Familial amyloidotic polyneuropathy (FAP) is the common form of hereditary generalized amyloidosis and is characterized by the accumulation of amyloid fibrils in the peripheral nerves and other organs. Liver transplantation has been utilized as a therapy for FAP, because the variant transthyretin (TTR) is predominantly synthesized by the liver, but this therapy is associated with several problems. Thus, we need to develop a new treatment that prevents the production of the variant TTR in the liver. In this study, we used HepG2 cells to show in vitro conversion of the TTR gene by single-stranded oligonucleotides (SSOs), embedded in atelocollagen, designed to promote endogenous repair of genomic DNA. For the in vivo portion of the study, we used liver from transgenic mice whose intrinsic wild-type TTR gene was replaced by the murine TTR Val30Met gene. The level of gene conversion was determined by real-time RCR combined with mutant-allele-specific amplification. Our results indicated that the level of gene conversion was approximately 11 and 9% of the total TTR gene in HepG2 cells and liver from transgenic mice, respectively. Gene therapy via this method may therefore be a promising alternative to liver transplantation for treatment of FAP.
Amyloid Neuropathies↗
Common origin of the Val30Met mutation responsible for the amyloidogenic transthyretin type of familial amyloidotic polyneuropathy.
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Amino Acid Substitution↗
CSF hypocretin levels in Guillain-Barré syndrome and other inflammatory neuropathies.
CSF hypocretin-1 was measured in 28 Guillain-Barré syndrome (GBS), 12 Miller-Fisher syndrome, 12 chronic inflammatory demyelinating polyneuropathy (CIDP), and 48 control subjects. Seven GBS subjects had undetectably low hypocretin-1 levels (<100 pg/mL). Hypocretin-1 levels were moderately reduced in an additional 11 GBS, 5 Miller-Fisher syndrome, and 1 CIDP subject. Low levels in GBS occurred early in the disease and were associated with upper CNS level abnormalities.
Adolescent↗
A Japanese family with FEOM1-linked congenital fibrosis of the extraocular muscles type 1 associated with spinal canal stenosis and refinement of the FEOM1 critical region.
We identified a Japanese family with congenital fibrosis of the extraocular muscles, including 24 affected individuals through five generations. To determine their form of congenital fibrosis of the extraocular muscles, we performed clinical and linkage studies. DNA typing for linkage to the FEOM1 (12p11.2-q12) and FEOM3 (16qter) loci was performed on genomic DNA, using fluorescent microsatellite polymorphic markers. All affected individuals shared the common manifestations of congenital fibrosis of the extraocular muscles type 1 including congenital ptosis, infraducted globe position in primary gaze, and upward gaze palsy in both eyes. Unexpectedly, we found apparent spinal canal stenosis in the cervical spine in all affected family members who were examined. Genetic analysis revealed linkage to the FEOM1 locus with a maximum lod score of 4.42 at theta of zero. One affected family member harbored a recombination event between D12S345 and D12S1692, narrowing the FEOM1 locus from the published 3-cM region flanked by D12S1584 and D12S1668 to a 2.1-cM region flanked by D12S345 and D12S1668. Thus, we have established that this family segregates congenital fibrosis of the extraocular muscles type 1 as an autosomal dominant trait and that their disorder both maps to and refines the FEOM1 locus. This is the first clinical and genetic report of such a family in the Japanese population and the first report of spinal involvement in congenital fibrosis of the extraocular muscles.
Adolescent↗
Isolation and characterization of psychrophiles producing cold-active beta-galactosidase.
AIMS: The present study was conducted to screen for psychrophilic micro-organisms that are able to hydrolyse lactose at low temperature, and to examine the cold-active beta-galactosidase produced by the isolated psychrophilic micro-organisms. METHODS AND RESULTS: Psychrophilic bacteria, which grow on lactose as a sole carbon source, were isolated from soil from Hokkaido, Japan. The phenotype and sequence of 16S rDNA of the isolated strains indicated a taxonomic affiliation to Arthrobacter psychrolactophilus. The isolated A. psychrolactophilus strains were able to grow on lactose at below 5 degrees C, and showed cold-active beta-galactosidase activity, which was highly specific at even 0 degrees C. CONCLUSIONS: Facts in this study may indicate the possibility that the isolated strains produce novel beta-galactosidases that are able to hydrolyse lactose at low temperature, although some strains have isozymes. SIGNIFICANCE AND IMPACT OF THE STUDY: It may be possible that the cold active beta-galactosidases from the isolated strains can be applied to the food industry, e.g. processing of milk and whey below 5 degrees C.
Arthrobacter↗
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and CADASIL-like disorders in Japan.
We reviewed 12 patients from 11 Japanese families diagnosed as having CADASIL from 1998 to 2001. The age of onset of focal neurologic deficits ranged from 38 to 71 years (mean: 50.4 +/- 9.8 years). Japanese CADASIL patients rarely had migraine and frequently presented with symptoms of dementia at diagnosis. Notch3 mutations were concentrated in exons 3, 4, and 5. Cysteine was replaced by another amino acid or vice versa in the majority of Japanese CADASIL patients. However, in 2 families, the mutations were not related to cysteine. In the prospective study, 2030 patients with stroke were hospitalized in 6 hospitals with stroke units in the Kumamoto district from 1999 to 2001. Among them, 14 patients fulfilled the criteria of being less than 60 years of age, showing lacunar strokes and/or TIA, presence of a family history, and no risk factors of stroke. One of these 14 patients was diagnosed as having CADASIL by DNA analysis. However, if hyperlipidemia was excluded from the list, 16 patients fulfilled the criteria and 2 patients were diagnosed as having CADASIL by DNA analysis. It was suspected that the incidence of CADASIL is not so rare in Japan. There were some families with CADASIL-like features, but without Notch3 mutations or GOM, suggesting the need for genetic analysis in the future.
Adult↗
CSF hypocretin/orexin levels in narcolepsy and other neurological conditions.
OBJECTIVE: To examine the specificity of low CSF hypocretin-1 levels in narcolepsy and explore the potential role of hypocretins in other neurologic disorders. METHODS: A method to measure hypocretin-1 in 100 microL of crude CSF sample was established and validated. CSF hypocretin-1 was measured in 42 narcolepsy patients (ages 16-70 years), 48 healthy controls (ages 22-77 years,) and 235 patients with various other neurologic conditions (ages 0-85 years). RESULTS: As previously reported, CSF hypocretin-1 levels were undetectably low (<100 pg/mL) in 37 of 42 narcolepsy subjects. Hypocretin-1 levels were detectable in all controls (224-653 pg/mL) and all neurologic patients (117-720 pg/mL), with the exception of three patients with Guillain-Barré syndrome (GBS). Hypocretin-1 was within the control range in most neurologic patients tested, including patients with AD, PD, and MS. Low but detectable levels (100-194 pg/mL) were found in a subset of patients with acute lymphocytic leukemia, intracranial tumors, craniocerebral trauma, CNS infections, and GBS. CONCLUSIONS: Undetectable CSF hypocretin-1 levels are highly specific to narcolepsy and rare cases of GBS. Measuring hypocretin-1 levels in the CSF of patients suspected of narcolepsy is a useful diagnostic procedure. Low hypocretin levels are also observed in a large range of neurologic conditions, most strikingly in subjects with head trauma. These alterations may reflect focal lesions in the hypothalamus, destruction of the blood brain barrier, or transient or chronic hypofunction of the hypothalamus. Future research in this area is needed to establish functional significance.
Carrier Proteins↗
Role of autonomic nervous system for development and suppression of motion sickness in Suncus murinus.
To clarify the role of autonomic nervous function in motion sickness, the effect of agents that act on the autonomic nervous system on the motion stimuli-induced emesis was studied in two strains of Suncus murinus (Jic:SUN-Her and Jic:SUN-Ler) with congenitally different sensitivity to veratrine sulfate. We demonstrated significant differences between the two strains in sensitivity to motion stimuli. Isoproterenol (2.5 mg kg(-1), s.c.) significantly prolonged the latency to the first emetic episode induced by motion stimuli and significantly decreased the number of emetic episodes in Jic:SUN-Her suncus. Hexamethoium (2.0 mg kg(-1), s.c.) tended to shorten the latency in Jic:SUN-Ler. Acetylcholine (1.2 mg kg(-1), s.c.) enhanced the emetic response in Jic:SUN-Ler, but atropine (4.0 mg kg(-1), s.c.) suppressed motion stimuli-induced emetic response in Jic:SUN-Her. These results suggest that the predominance of parasympathetic nervous activity is relevant to the enhancement of motion stimuli-induced emetic response, whereas the predominance of sympathetic nervous activity suppresses motion stimuli-induced emetic response. Norepinephrine (0.8 mg kg(-1), s.c.) enhanced motion stimuli-induced emesis contrary to isoproterenol in Jic:SUN-Ler although both drugs are adrenergic agents. However, atropine pretreatment (4.0 mg kg(-1), s.c.) inhibits norepinephrine-induced emetic response. It was considered that norepinephrine-induced emetic response might be dependent on a secondary increase of parasympathetic nervous activity due to bororeflex. Moreover, the different emetic response in Jic:SUN-Her and Jic:SUN-Ler suncus to motion stimuli and drug administration mentioned above indicated that different participation of autonomic nervous activity and/or afferent information from the baroreceptor in the emetic response may exist between these animal groups.
Acetylcholine↗
Impaired production of naive T lymphocytes in human T-cell leukemia virus type I-infected individuals: its implications in the immunodeficient state.
Opportunistic infections frequently occur in patients with adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I) carriers. However, the underlying mechanisms of such infections remain unknown. To clarify the mechanism of immunodeficiency in those infected with HTLV-I, this study analyzed the T-cell subsets in HTLV-I carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis and ATL using 3-color fluorescence with CD62L and CD45RA coexpression either with CD4(+) or CD8(+) T cells. The number of naive T lymphocytes was markedly suppressed in patients with ATL, particularly in those with acute form, compared with uninfected control individuals. The number of naive T cells was low in HTLV-I-infected individuals under 50 years old compared with uninfected individuals, whereas the number of memory T lymphocytes was greater in HTLV-I-infected individuals. Although the increase of memory T lymphocytes correlated with HTLV-I provirus loads, no relationship was found between naive T-cell counts and provirus loads. T-cell receptor rearrangement excision circles (TRECs), which are generated by DNA recombination during early T lymphopoiesis, were quantified to evaluate thymic function in HTLV-I-infected individuals. TREC levels were lower in HTLV-I-infected individuals than in uninfected individuals. In HTLV-I carriers less than 70 years old, an increase of Epstein-Barr virus DNA in peripheral blood mononuclear cells was observed in 6 of 16 (38%) examined, whereas it was detectable in only 1 of 11 uninfected controls. These results suggested that the low number of naive T lymphocytes was due to suppressed production of T lymphocytes in the thymus, which might account for immunodeficiency observed in HTLV-I-infected individuals.
CD4-Positive T-Lymphocytes↗